PMID- 34678474
OWN - NLM
STAT- MEDLINE
DCOM- 20220117
LR  - 20221221
IS  - 1878-1519 (Electronic)
IS  - 1569-9048 (Print)
IS  - 1569-9048 (Linking)
VI  - 296
DP  - 2022 Feb
TI  - Mechano-inflammatory sensitivity of ACE2: Implications for the regional 
      distribution of SARS-CoV-2 injury in the lung.
PG  - 103804
LID - S1569-9048(21)00190-7 [pii]
LID - 10.1016/j.resp.2021.103804 [doi]
AB  - The coronavirus disease (COVID-19) caused by SARS-CoV-2 can result in severe 
      injury to the lung. Computed tomography images have revealed that the virus 
      preferentially affects the base of the lung, which experiences larger tidal 
      stretches than the apex. We hypothesize that the expression of both the 
      angiotensin converting enzyme-2 (ACE2) receptor for SARS-CoV-2 and the 
      transmembrane serine protease 2 (TMPRSS2) are sensitive to regional cell stretch 
      in the lung. To test this hypothesis, we stretched precision cut lung slices 
      (PCLS) for 12 h with one of the following protocols: 1) unstretched (US); 2) 
      low-stretch (LS), 5% peak-to-peak area strain mimicking the lung base; or 3) 
      high-stretch (HS), the same peak-to-peak area strain superimposed on 10% static 
      area stretch mimicking the lung apex. PCLS were additionally stretched in 
      cigarette smoke extract (CSE) to mimic an acute inflammatory exposure. The 
      expression of ACE2 was higher whereas that of TMPRSS2 was lower in the control 
      samples following LS than HS. CSE-induced inflammation substantially altered the 
      expression of ACE2 with higher levels following HS than LS. These results suggest 
      that ACE2 and TMPRSS2 expression in lung cells is mechanosensitive, which could 
      have implications for the spatial distribution of COVID-19-mediated lung injury 
      and the increased risk for more severe disease in active smokers and patients 
      with COPD.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Bartolak-Suki, Erzsebet
AU  - Bartolak-Suki E
AD  - Department of Biomedical Engineering, Boston University, Boston, MA, United 
      States.
FAU - Mondonedo, Jarred R
AU  - Mondonedo JR
AD  - Department of Thoracic Surgery, University of Michigan, Ann Arbor, MI, United 
      States.
FAU - Suki, Bela
AU  - Suki B
AD  - Department of Biomedical Engineering, Boston University, Boston, MA, United 
      States. Electronic address: bsuki@bu.edu.
LA  - eng
GR  - U01 HL139466/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20211019
PL  - Netherlands
TA  - Respir Physiol Neurobiol
JT  - Respiratory physiology & neurobiology
JID - 101140022
RN  - EC 3.4.17.23 (Ace2 protein, rat)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Angiotensin-Converting Enzyme 2/*biosynthesis
MH  - Animals
MH  - Cells, Cultured
MH  - Lung/cytology/*metabolism
MH  - Lung Injury/*metabolism
MH  - Male
MH  - Mechanotransduction, Cellular/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - SARS-CoV-2/*metabolism
PMC - PMC8524802
OTO - NOTNLM
OT  - Gravity
OT  - Mechanotransduction
OT  - Receptor expression
OT  - Stretch
EDAT- 2021/10/23 06:00
MHDA- 2022/01/18 06:00
PMCR- 2021/10/19
CRDT- 2021/10/22 20:34
PHST- 2021/09/14 00:00 [received]
PHST- 2021/10/12 00:00 [revised]
PHST- 2021/10/17 00:00 [accepted]
PHST- 2021/10/23 06:00 [pubmed]
PHST- 2022/01/18 06:00 [medline]
PHST- 2021/10/22 20:34 [entrez]
PHST- 2021/10/19 00:00 [pmc-release]
AID - S1569-9048(21)00190-7 [pii]
AID - 103804 [pii]
AID - 10.1016/j.resp.2021.103804 [doi]
PST - ppublish
SO  - Respir Physiol Neurobiol. 2022 Feb;296:103804. doi: 10.1016/j.resp.2021.103804. 
      Epub 2021 Oct 19.